Elements: Models and tools for on-line design and simulations for DNA and RNA nanotechnology

DNA和RNA纳米技术是使用DNA和RNA分子作为构建自组装纳米结构和器件的基本构建块的快速发展的领域。有前途的应用包括用于诊断、药物递送、纳米光子学、生物物理学研究和蛋白质结构生物学的新材料，以及用于执行分子计算的设备。这些结构的开发目前是通过试错法完成的，这是昂贵且耗时的，因为每个新设计都必须进行实验测试并逐渐优化，直到实现所需的结构。计算机模拟可以深入了解这些系统的组装和功能，大大简化和加速设计过程，并指导对纳米结构功能的理解。然而，计算机模拟需要分子模拟的专业知识和高性能的计算基础设施，是不容易访问的实验组。在这个项目中，我们将开发一个新的Web服务器，为用户提供在线自动化工具，可用于设计，模拟和分析DNA和RNA纳米结构的特性。该网络服务器还将包含以前报道的纳米结构的存储库，以便研究人员可以轻松地访问和使用现有的设计并对其进行调整。我们还将开发混合DNA/RNA和蛋白质-DNA/RNA纳米结构的新模型，从而将计算设计和验证的能力扩展到更大和更复杂的纳米结构。该项目将通过创建一个高效的集成平台来存储，编辑，设计和计算分析纳米结构，从而为从事纳米技术的团体提供共同的资源，同时将这些纳米结构的访问扩展到其他领域的研究人员，从而使公众受益。最终的结果将是加速和整合纳米技术的发展，简化设计过程，并促进生物分子纳米结构的实际应用。 这些工具也将对模拟方法的教学和推广活动产生影响，学生将通过使用这些工具设计自己的纳米结构来学习模拟和自组装的原理。尽管在开发允许组装和表征DNA和RNA纳米结构的实验方法方面取得了重大进展，但缺乏用于设计纳米结构的易于使用的软件工具仍然是在其他相关领域中更广泛采用DNA和RNA纳米技术的主要瓶颈。该领域需要新的结构设计和验证方法来充分发挥其潜力。此外，杂交DNA-蛋白质和RNA-蛋白质纳米技术的新生领域目前缺乏允许模拟的有效粗粒度工具。该提案将包括：1）创建一个基于网络的DNA/RNA纳米结构交互式设计平台，沿着一个可公开访问的网络服务器，用于模拟和分析核酸纳米技术; 2）创建一个公共在线存储库，存储来自该领域的成功组装和验证的DNA和RNA纳米结构，研究人员将能够共享和编辑已发表的设计，允许纳米结构的容易共享和扩展; 3）扩展我们先前开发的DNA和RNA模型，以包括蛋白质和DNA-RNA杂交体的粗粒度表示，从而能够设计杂交蛋白质-DNA/RNA纳米材料。该项目将需要开发新的纳米结构可视化和分析方法，并在GPU卡上进行交互式高性能模拟，以及根据混合纳米结构的新实验数据对新模型进行参数化。这项研究将产生重大的社会和教育影响。用户友好的设计工具将很容易纳入研究生和本科课程。我们还将把这些工具纳入我们在高中学生和教师中的推广活动。该在线设计工具将用于基于网络的纳米结构设计竞赛的众包科学。该奖项反映了NSF的法定使命，并且通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

DNA and RNA nanotechnology are rapidly developing fields that use DNA and RNA molecules as basic building blocks for constructing self-assembled nanoscale structures and devices. Promising applications include novel materials for diagnostics, drug delivery, nanophotonics, biophysical studies, and protein structural biology, as well as devices to perform molecular computation. Development of these structures is currently done with a trial-and-error approach, which is costly and time consuming because each new design has to be experimentally tested and gradually optimized until the desired structure is achieved. Computer simulations can provide insight into the assembly and function of these systems and greatly simplify and accelerate the design process, as well as guide understanding of the nanostructure function. However, computer simulations require molecular simulation expertise and high performance computing infrastructures that are not readily accessible to experimental groups. In this project, we will develop a new web server to provide users with online automatized tools that can be used to design, simulate, and analyze the properties of DNA and RNA nanostructures. The web server will also contain a repository of previously reported nanostructures so that researchers can easily access and use existing designs and adapt them for their use. We will also develop new models for hybrid DNA/RNA and protein-DNA/RNA nanostructures, thereby extending the ability of computational design and verification to larger and more complex nanostructures. This project will benefit the public by creating a highly efficient integrated platform to store, edit, design and computationally analyze nanostructures, thus providing a common resource to groups working in nanotechnology while simultaneously expanding access to these nanostructures to researchers in other fields. The net result will be to speed up and integrate the development of nanotechnology, simplify the design process, and facilitate the extension of biomolecular nanostructures to practical applications. The tools will also be impactful for teaching the simulation methods and for outreach activities, where students will be taught the principles of simulation and self-assembly by using the tools to design their own nanostructures. Despite significant progress in the development of experimental methods that allow for assembly and characterization of the DNA and RNA nanostructures, the lack of easy-to-use software tools for design of nanostructures still remain a major bottleneck for wider adoption of the DNA and RNA nanotechnology in other related fields. Novel methods for structure design and verification are needed for the field to reach its full potential. Furthermore, the nascent field of hybrid DNA-protein and RNA-protein nanotechnology currently lacks efficient coarse-grained tools that would allow for the simulation. This proposal will consist of 1) Creation of a web-based platform for the interactive design of DNA/RNA nanostructures, along with a publicly accessible webserver for simulations and analysis of nucleic acid nanotechnology; 2) Creation of a public online repository of successfully assembled and verified DNA and RNA nanostructures from the field, where researchers will be able to share and edit published designs, allowing easy sharing and extensions of nanostructures; 3) Extension of our previously developed models of DNA and RNA to include coarse-grained representation of proteins and DNA-RNA hybrids, thus enabling the design of hybrid protein-DNA/RNA nanomaterials. The project will require development of new methods for nanostructure visualizations and analysis coupled with interactive high performance simulations on GPU cards, and parametrization of new models on new experimental data of hybrid nanostructures. The proposed research will have significant societal and educational impact. The user-friendly design tool will be easily incorporated into both the graduate and undergraduate curriculum. We will also incorporate the tools also into our outreach activities among high school students and teacher. The online design tool will be used for crowd-sourced science for web-based nanostructure design competitions.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.